Carbonyl reductase 1 (CBR1) has been reported to be involved in cancer progression. Recently, we found that CBR1 overexpression inhibited malignant behaviors and the epithelial mesenchymal transition (EMT) in uterine cervical cancer. It remained unclear whether this was also the case in uterine leiomyosarcoma (uLMS), which is derived from mesenchymal cells and is a much more malignant gynecological tumor. A number of previous studies suggested that malignant behaviors are associated with EMT, even in mesenchymal malignant tumors. In the present study, we investigated whether CBR1 inhibits malignant behaviors and EMT in uLMS. We established clones of uLMS cells (SKN cells) and uterine sarcoma cells (MES-SA cells) that overexpressed CBR1. Cell proliferative, migratory and invasive activities were suppressed by CBR1 overexpression, accompanied by increases in the expressions of epithelial markers (E-cadherin and cytokeratin) and decreases in the expressions of mesenchymal markers (N-cadherin and fibronectin), suggesting that CBR1 overexpression inhibits malignant behaviors and EMT in uLMS cells. In addition, transforming growth factor-β (TGF-β) production and the subsequent signaling and phosphorylation of Smad were suppressed in the clones. To investigate the association between TGF-β and EMT, SKN cells were treated with TGF-β or a TGF-β receptor blocker (SB431542). EMT was promoted by TGF-β and inhibited by SB431542. In conclusion, this is the first study, to the best of the authors' knowledge, showing that CBR1 overexpression inhibits malignant behaviors and EMT in uLMS cells. The present study provided novel insight demonstrating that the suppressive effect of CBR1 is mediated through TGF-β signaling.

No abstract

Purpose To identify the aberrantly expressed long non‐coding RNAs (lncRNAs) in ovarian high‐grade serous carcinoma (HGSC). Methods Total RNA was isolated in HGSC cell lines, ovarian surface epithelial cells, and normal ovaries. Aberrantly expressed lncRNAs in HGSC were identified by PCR array, which analyzes 84 kinds of lncRNAs. To infer their functions, HGSC cell lines with different levels of expression of the identified lncRNAs were established, and then, activities of proliferation, migration, and apoptosis were examined. Expression levels of the identified lncRNAs were also examined in multiple ovarian HGSC tissues. Results Ten aberrantly expressed lncRNAs, six upregulated and four downregulated, were identified in the HGSC cell lines. The authors established four HGSC cell lines: in two of the cell lines, one of the upregulated lncRNAs was knocked down, and in two other cell lines, one of the downregulated lncRNAs (MEG3 and POU5F1P5) was overexpressed. Migration activities were inhibited in the HGSC cell lines overexpressing MEG3 or POU5F1P5 while there were no differences in proliferation and apoptosis between the established and control cell lines. The four lncRNAs downregulated in the HGSC cell lines were also observed to be downregulated in ovarian HGSC tissues. Conclusion The authors identified four downregulated lncRNAs in ovarian HGSC.